Delayed Cord Clamping
T. Flint Porter, MD, MPH
Disclosure
• I had an umbilical cord
• I sometimes receive remuneration for
clamping and cutting umbilical cords
− I believe this is appropriate
• Legal Department:
− I’m kidding, this is a joke, I’m kidding.
− Nothing to disclose
IMC Parking Lot
Background
• Placental transfusion: blood volume
transfused to baby after delivery
• Umbilical Cord Blood Flow (UCBF)
• Factors that influence transfusion
− Delayed cord clamping (DCC)
− Cord milking (MUC)
− Gravity
− Uterotonics
Mechanisms of DCC and
Improved Outcome
• Increased neonatal blood volume
− Improved perfusion
− Reduction in organ injury
• Allow spontaneous breathing to begin
− Smoother transition of cardiopulmonary
and cerebral circulation
− Reduce need for resuscitation
• Increase iron stores, reduce anemia
• Transfusion of blood enriched with
stem cells and immunoglobulin
Potential Drawbacks
• Delayed resuscitation
• Increase risk of neonatal
hypothermia, polycythemia,
hyperbilirubinemia
• Increase risk for maternal
hemorrhage
• Interfere with cord blood collection
How long does umbilical cord
blood flow continue?
• Prospective observational trial of UCBF
after delivery in 30 term infants
• Protocol
− Placed skin-to-skin by CNM
− Doppler of straight portion until clamping
− Cord clamped at CNM discretion (pulsation)
− Pulse cessation determined by researcher
− Measurements after 1st breath (30/30) and
oxytocin (28/30)
Boere et al, Arch Dis Child Fet Neo Ed, 2014
UCBF After Delivery
Venous Flow
3/30 (10%)
• No venous flow at initial
exam
17/30 (57%)
• Flow stopped 04:36 (03:03–08:22)
• Cord clamped 06:02 (04:47–09:35)
10/30 (33%)
• Flow still present when cord
clamped 05:13 (02:56–09:15)
Boere et al, Arch Dis Child Fet Neo Ed, 2014
UCBF After Delivery
Venous Flow
Breathing
• Flow stopped during
deep breaths
Crying
• Flow stopped
• Flow reversed flow
with “hard” crying
UCBF After Delivery
Arterial Flow
5/30 (17%)
• No flow at initial exam
12/30 (40%)
• Flow stopped 04:22 (02:29–07:17)
• Cord clamped 06:15 (05:02–09:30)
13/30 (43%)
• Flow still present when cord
clamped 05:16 (03:32–10:10)
UCBF After Delivery
Time Differences
In 15 infants arterial and venous
flow stopped simultaneously
7 infants
Arterial stopped first
01:08 (00:51–03:03)
8 infants
Venous stopped first
01:43 (00:51–02:45)
• Flow to baby
• Net flow from
baby!
UCBF After Delivery
Conclusions
• UCBF longer than previously described
• Complex process affected by
− Breathing and crying
− Differing arteriovenous flow cessation
− Arterial flow toward the placenta
• UCBF unrelated to pulsations…
reconsider as a time point for cord
clamping
Term Infants
Cochrane 2013
• 15 RCTs of 3911 women > 37 weeks
• Clamping Groups
1. < 60 seconds after delivery
2. > 60 seconds after delivery or pulse cessation
• Primary outcomes
− PP hemorrhage
− maternal and neonatal mortality
• Secondary outcomes
− Maternal blood loss and related morbidity
− Neonatal morbidity
Term Infants
Cochrane 2013
• Severe PPH or mortality
• Maternal blood loss
• Apgar scores
• NICU admission
• RDS
• Polycythemia
Term Infants
Cochrane 2013
Hemoglobin (g/dL)
Newborn
24 – 48 hours
-2.17 g/dL (-4.06 to -0.28)
-1.49 g/dL (-1.78 to -1.21)
3 – 6 months
No difference
Iron Deficiency
(3-6 months)
Jaundice
Phototherapy
Clinical jaundice
2.7 (1.04 to 6.7)
0.62 (0.41 to 0.96)
0.84 (0.66 to 1.07) ND
Term Infants
Cochrane 2013
Authors’ Conclusion
• “DCC in healthy term infants appears to
be warranted… growing evidence that
DCC increases early hemoglobin
concentrations and iron stores...
• … as long as access to treatment for
jaundice requiring phototherapy is
available.”
Iron and Neuro. Status at 1 Year
Andersson, JAMA Ped 2014
• Randomized controlled trial of DCC in
full term infants
• Groups
− Delayed: >180 secs after delivery
− Early: < 10 secs after delivery
• Outcomes
− Ferritin levels at 12 months
− Neurodevelopment at 12 months assessed
by ASQ (Ages and Stages Questionnaire)
Iron and Neuro. Status at 1 Year
Andersson, JAMA Ped 2014
Cord Clamping
Measure
Hb
Hematocrit
Ferritin
DCC (174)
ECC (163)
P
11.8
12.0
NS
35
35
NS
35.4
33.6
NS
Proportion with Iron Status Outside Norm (%)
Anemia
16.1
11.6
NS
Iron deficiency
3.4
5.4
NS
Iron and Neuro. Status at 1 Year
Andersson, JAMA Ped 2014
Proportion of infants with low ASQ Scores (%)
Cord Clamping
ASQ Measure
DCC (174)
ECC (163)
P
Communication
3.5
3.6
NS
Gross Motor
5.9
4.8
NS
Fine Motor
6.5
4.2
NS
Problem Solving
4.1
2.4
NS
Personal-Social
5.9
4.2
NS
DCC in Term Infants, F/U at Age 4
Anderson et al, JAMA Ped 2015
• Iron deficiency associated with poor
neurodevelopmental outcome
• Follow up study at 4 years
• Outcomes
− “Full scale” IQ (Primary Outcome)
− Fine motor testing (Movement ABC)
− Ages and Development (ASQ)
− Behavior (SDQ)
DCC in Term Infants, F/U at Age 4
Anderson et al, JAMA Ped 2015
Primary Outcome
• Full scale IQ scores: No difference
• Low IQ (<85): No difference
• No difference in verbal, performance,
processing speed, or general language
DCC in Term Infants, F/U at Age 4
Anderson et al, JAMA Ped 2015
Secondary Outcomes
Movement ABC – Proportion with low test scores
Delayed (%) Early (%) P Value
Manual dexterity
18
26
NS
Coins in box
30
35
NS
Bead threading
16
20
NS
Drawing bike trail
4
13
0.02
DCC in Term Infants, F/U at Age 4
Anderson et al, JAMA Ped 2015
ASQ – Proportion with low test scores
Delayed (%) Early (%) P Value
Communication
8.3
4.3
NS
Gross Motor
5.2
6.7
NS
Fine motor
3.7
11.0
0.03
Problem solving
5.2
8.5
NS
Personal/Social
3.0
8.4
0.006
Pencil Grip
13.2
25.6
0.01
DCC in Term Infants, F/U at Age 4
Anderson et al, JAMA Ped 2015
Gender Differences
DCC in Term Infants, F/U at Age 4
Anderson et al, JAMA Ped 2015
• Reduction in children with low scores
in fine motor and social domains
• Boys have the most improved results
− Fine motor skills
• Optimizing the time to cord clamping
may effect neurodevelopment in a low
risk population of children born in high
income countries.
Editorial Comment
JAMA Ped 2015
“The potential benefit of improving
maternal and neonatal care by a simple
no-cost intervention of delayed CC
should be championed by the
international community beginning now
and leading into the next decade.”
DCC in Term Infants
•
•
•
•
Conclusions
Iron deficiency
Long term effects, possible
Doesn’t matter if you keep the baby
below the placenta…
How long to wait? For the cord to
stop pulsating?
Preterm Infants
Preterm Infants
Cochrane 2012
• 15 studies, 738 infants, < 37 weeks
• Study Groups
− Immediate
− Placental transfusion strategies:
Delayed (≥ 30 - 120 seconds)
Cord milking
• Outcomes
− Death, severe IVH, PVL, neurodevelopment
Preterm Infants
Cochrane 2012
•
•
•
•
Neonatal death
Severe IVH
PVL
Neurodevelopmental
outcome
Preterm Infants
Cochrane 2012
Secondary
Outcomes
RR (95% CI)
Inotropic support
0.42, (0.23 to 0.77)
NEC
0.62, (0.43 to 0.90)
Transfusion
0.61 (0.46 to 0.81)
Phototherapy
1.21 (0.94 to 1.55)
Preterm Infants
Cochrane 2012
•
•
•
•
•
Authors’ Conclusion
Less need for transfusion
Better circulatory stability
Less IVH (all grades)
Lower NEC
Insufficient data for reliable
conclusions about any of the primary
outcomes
Placental Transfusion in VPN
Backes et al, OG 2014
• Systematic review and meta-analysis of DCC
and MUC < 32 week neonates (28 wks)
• RCTs with the following interventions
− Early clamping: < 15 seconds
− DCC: at least 20 seconds
− MUC: milking at least 3 times
• Outcomes
−
−
−
−
Maternal and obstetric
Safety
Hematological status
Neonatal Outcomes
Placental Transfusion in VPN
Backes et al, OG 2014
Safety
Variables
RCT #
MD (95% CI)
P
BP (4 hours)
4
3.24 (1.76, 4.72)
<.01
Apgar5
4
-0.07 (-.48, 0.33)
NS
Temp
3
0.02 (-.18, 0.22)
NS
Placental Transfusion in VPN
Backes et al, OG 2014
Hematologic
Outcomes
RCT
#
RR (95% CI)
P
Transfusion
6
0.75 (0.63, 0.90)
<.01
MD (95% CI)
Transfusion (#)
6
-1.14 (-2.01, 0.27) <.01
Hematocrit (1st)
10
4.49 (2.48, 6.5)
<.01
Bilirubin
8
0.53 (-0.01, 1.07)
0.05
Placental Transfusion in VPN
Backes et al, OG 2014
Neonatal
Outcomes
RCT # Risk Ratio (95% CI)
P
Total IVH
9
0.62 (0.43,0.91)
<.01
Severe IVH
6
0.64 (0.34, 1.21)
NS
NEC
4
0.55 (0.23, 1.31)
NS
Sepsis
5
0.73 (0.44, 1.20)
NS
Mortality
8
0.42 (0.19, 0.95)
.04
DCC in Preterm Neonate
Elimian et al, OG 2014
• RCT of DCC for neonates 24-34 weeks
• Groups
− < 5 seconds
− > 30 seconds (3-4 passes of milking allowed)
• Intention to treat
• Primary outcome
− Need for transfusion (hb < 10 or symptomatic)
• Secondary outcomes
− Hematocrit and IVH
DCC in Preterm Neonate
Elimian et al, OG 2014
Clamping
Outcome
Delayed (99)
Immediate (101)
P
Transfusion
25 (25.3)
24 (23.7)
.80
Anemia
36 (36.4)
48 (47.5)
.11
Phototherapy
55 (55.6)
55 (54.5)
.89
IVH (grade III)
3 (3.0)
3 (3.0)
1.0
Cord Milking in ELGANs
Patel et al, AJOG 2014
• MUC provides benefits of placental transfusion
but avoids delay in resuscitation
• Cohort study of outcomes < 30 weeks
− MUC from 9/2011 – 8/2013
− Historical EGLANs from 1/2010-8/2011
• Composite outcome
− IVH, NEC, death before discharge
• Improvement in markers of hemodynamic
stability
MUC in ELGANs
Patel et al, AJOG 2014
MUC Procedure
• Neonate held 10 cm below placenta
• Twisting and nuchal cords released
• Milking technique
− Pinched close to the placenta
− Milked over 2-3 seconds X 3
− Pause for 2-3 seconds between milking
− Total procedure < 30 seconds
MUC in ELGANs
Patel et al, AJOG 2014
100%
Control (160)
MUC (158)
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
PRBC
Dopamine
NEC
Severe IVH
Death
Composite
MUC in ELGANs
Patel et al, AJOG 2014
Effect of MUC on Mean BP First Day of Life
45
40
P < 0.01
Control
MUC
P < 0.01
P < 0.01
35
30
25
20
15
10
5
0
0-6 hours
6-12 hours
12-24 hours
DCC with and without MUC
Krueger, AJOG 2015
• RCT
− DCC: 30 second delay in cord clamping
− DCC + MUC (4 times, 4-5 sec. between)
• 24 – 31 6/7 weeks
− Stratified results by gestational age
• Primary outcome: hematocrit
• Secondary outcomes
− Mortality, days on ventilator, LOS, peak
bilirubin, days of phototherapy, “neonatal
complications
DCC with and without MUC
Krueger, AJOG 2015
• No difference in primary outcome
− Hematocrit
• No difference in secondary outcomes
− Bilirubin
− Phototherapy
− Days on ventilator
− Length of stay
− Other neonatal morbidities
• MUC added nothing to DCC
Placental Transfusion Strategies
Conclusions for Preterm Babies
• Seems to improve short term outcomes
− Longer term?
• Better for < 30 weeks
• Inconsistent findings among latest
round of trials
− Different protocols
• MUC as good as DCC?
− May be easier in high risk settings
Summary from AAP/AHA
Neonatal Resuscitation Program (NRP®)
• Current evidence suggests that cord
clamping should be delayed for at least 3060 seconds for most vigorous term and
preterm newborns.
• There is insufficient evidence to recommend
an approach to cord clamping for newborns
who require resuscitation at birth.
© World Health Organization
Delayed umbilical cord clamping for improved
maternal and infant health and nutrition outcomes
(2014)
• “The cord should not be clamped
earlier than 1 min after birth.”
• Regardless of route of delivery
• Regardless of gestational age
• Stimulation before cord clamping
• “…the cord is not clamped in the first
60 seconds…
• The cord should be clamped before 5
minutes, although women should be
supported if they wish this to be
delayed further.”
ACOG Committee Opinion
Number 543, 2012 (reaffirmed 2014)
• “Currently, insufficient evidence exists
to support or to refute the benefits from
DCC for term infants that are born in
settings with rich resources.”
• “Evidence supports DCC in preterm
infants.”
What do I think?
“Perinatal medicine is replete with
examples of promising interventions
the short-term benefits of which did
not translate into long-term benefits,
including some that caused harm.”
Tarnow-Mordi et al, AJOG 2014
Gravity
Vain et al, Lancet, 2014
• RCT in Argentina
− All had DCC for 2 mins after NSVD
− Introitus vs. Abdomen
• Primary outcome was weight
− Proxy for volume of placental transfusion
• Procedure
− Weighed < 15 secs of delivery
− Weighed again at 2 mins after
Gravity
Vain et al, Lancet, 2014
Introitus (197)
Abdomen (194)
Mean Weight
Change
Mean Weight
Change
Difference
P
56
53
3 (–5.8-12.8)
NS
It doesn’t matter where you hold
the baby.
Purported Advantages
• Preterm infants
− Decreased RDS
− Decrease need for transfusion
(60-80% of < 32 weeks get transfusion)
− Less IVH
• Term infants
− Less iron deficiency
− Long term outcomes improved (?)
MUC in ELGANs
Patel et al, AJOG 2014
Resuscitation Characteristics
Variable
Historical (160)
MUC (158)
P
Gestation
27.1
27.4
0.10
Birthweight
880
960
0.009
Temp on admit
36.3
36.5
NS
20 (13%)
34 (22%)
NS
Chest compress.
8 (5%)
10 (6%)
NS
Intubation (mins)
5
6
NS
Surfactant (mins)
29
38
NS
Max resuscitation*
*blow by oxygen, positive airway pressure, positive pressure
MUC in ELGANs
Patel et al, AJOG 2014
Neonatal Outcomes < 30 Weeks
Variable
Control (160)
MUC (158)
P
45.1 ± 7.4
49.9 ± 5.5
<.01
PRBC
127 (79)
90 (57)
<.01
Dopamine <72
51 (32)
28 (18)
<.01
NEC*
32 (20)
18 (11
<.05
Severe IVH
27 (17)
15 (10)
<.05
Death or IVH
40 (25)
22 (14)
<.05
Composite
63 (39)
34 (22)
<.01
Hematocrit